title: Dual immunostaining of cervical cytology specimens with atypical squamous cells for p16/Ki-67 does not exclude the existence of a high-grade squamous intraepithelial lesion.
abstract: This study was conducted to evaluate the accuracy of p16/Ki-67 dual immunostaining compared to high-risk human papillomavirus (HR-HPV) DNA testing for cervical intraepithelial neoplasia (CIN) in women with atypical squamous cells, cytology not excluding high-grade squamous intraepithelial lesion (ASC-H). Data were collected from 73 patients diagnosed to have ASC-H on a Pap smear who were HPV genotyped and had histological examination of a cervical biopsy. The CINtecPLUS kit was used on residual liquid-based material, and the immunoreactivity of dual-stained cells was graded according to the number as follows: G1 (1-5 positive cells), G2 (6-10), G3 (11-20), and G4 (> 20). Accuracy was evaluated based on the histological examination of colposcopy-guided biopsy or cervical conization on follow-up. Of the 70 patients with available data, positive p16/Ki-67 was associated with histological severity as follows: 15% in negative histology, 67% in CIN 1, 90% in CIN 2, and 100% in CIN 3. The average grade of positive p16/Ki-67 staining also increased from 0.2 in histologically negative cases to 1.2 in CIN 1, 2.4 in CIN 2, and 2.9 in CIN 3 (p < 0.01). For patients with CIN 2 or higher, p16/Ki-67 had a sensitivity of 94.6% and a specificity of 75.8%, while HR-HPV testing showed a sensitivity of 67.6% and a specificity of 66.7%. p16/Ki-67 immunostaining demonstrated better accuracy than HR-HPV for detecting CIN 2 or higher in patients with ASC-H cytology. Given the higher concordance with histological diagnosis, the grading system of positive p16/Ki-67 can be a useful adjunct for predicting high-grade lesions in clinical practice.
authors.affiliation: Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, South Korea.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Koo
authors.forename: Ho-Suap
authors.initials: HS
authors.lastname: Hahn
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Lee
authors.forename: Kyung-Taek
authors.initials: KT
authors.lastname: Lim
authors.forename: Ki-Heon
authors.initials: KH
authors.lastname: Lee
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Kim
authors.forename: Yi-Kyeong
authors.initials: YK
authors.lastname: Chun
authors.forename: Hy-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Sung-Ran
authors.initials: SR
authors.lastname: Hong
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D003127:Colposcopy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000821:virology; D012680:Sensitivity and Specificity; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000821:virology / Q000378:metabolism* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen